tbuckley/cabot-search huggingface dataset:
Annals Graphic Medicine - Advocating for Diastole
Authors: Ankit Mehta, Tseganesh Selameab
Journal: Annals of Internal Medicine (2023)

Web ExclusivesApril 2023Annals Graphic Medicine - Advocating for DiastoleFREEAnkit Mehta, MD and Tseganesh Selameab, MDAnkit Mehta, MDMinneapolis, Minnesota (A.M.)Search for more papers by this author and Tseganesh Selameab, MDSt. Paul, Minnesota (T.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G22-0035 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Ankit Mehta, MD; Tseganesh Selameab, MDAffiliations: Minneapolis, Minnesota (A.M.)St. Paul, Minnesota (T.S.)Acknowledgment: This work was presented in part in: Selameab T, Mehta A, Clark C. Advocating diastole [video]. From: “Speaking of Race.” Art + Medicine. TPT-Twin Cities PBS and the Center for the Art of Medicine at the University of Minnesota Medical School. 29 April 2022. Available at https://video.tpt.org/video/advocating-diastole-hhbapt/ (accessed 22 September 2022).Disclosures: The authors have reported no disclosures of interest. The forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G22-0035.Author/Illustrator Information: Ankit Mehta, MD, is an illustrator, a graphic medicine enthusiast, a hospitalist with HealthPartners, and an Assistant Professor at the University of Minnesota Medical School (e-mail, [email protected]com). Tseganesh Selameab, MD, is an Assistant Professor at the University of Minnesota Medical School (e-mail, [email protected]com).This article was published at Annals.org on 28 March 2023. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Current IssueApril 2023Volume 176, Issue 4 ePublished: 28 March 2023 Issue Published: April 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
ABCB1 and ABCG2 Regulation at the Blood-Brain Barrier: Potential New Targets to Improve Brain Drug Delivery
Authors: Julia A. Schulz, Anika M.S. Hartz, Björn Bauer
Journal: Pharmacological Reviews (2023)

The drug efflux transporters ABCB1 and ABCG2 at the blood-brain barrier limit the delivery of drugs into the brain. Strategies to overcome ABCB1/ABCG2 have been largely unsuccessful, which poses a tremendous clinical problem to successfully treat CNS diseases. Understanding basic transporter biology, including intracellular regulation mechanisms that control these transporters, is critical to solve this clinical problem. In this comprehensive review, we summarize current knowledge on signaling pathways that regulate ABCB1/ABCG2 at the blood-brain barrier. In part I, we give a historical overview on blood-brain barrier research and introduce the role ABCB1 and ABCG2 play in this context. In part II, we summarize the most important strategies that have been tested to overcome the ABCB1/ABCG2 efflux system at the blood-brain barrier. In part III, the main component of this review, we provide detailed information on the signaling pathways that have been identified to control ABCB1/ABCG2 at the blood-brain barrier and their potential clinical relevance. This is followed by part IV, where we explain the clinical implications of ABCB1/ABCG2 regulation in the context of CNS disease. Lastly, in part V, we conclude by highlighting examples of how transporter regulation could be targeted for therapeutic purposes in the clinic. <b>Significance Statement</b> The ABCB1/ABCG2 drug efflux system at the blood-brain barrier poses a significant problem to successful drug delivery to the brain. Here, we review signaling pathways that regulate blood-brain barrier ABCB1/ABCG2 and could potentially be targeted for therapeutic purposes.
Drug Repurposing and Observational Studies: The Case of Antivirals for the Treatment of COVID-19
Authors: Miguel A. Hernán, Julia del Amo
Journal: Annals of Internal Medicine (2023)

Remdesivir and molnupiravir were the only 2 repurposed antivirals that were approved for emergency use during the COVID-19 pandemic. Both drugs received their emergency use authorization on the basis of a single industry-funded phase 3 trial, which was launched after evidence of in vitro activity against SARS-CoV-2. In contrast, for tenofovir disoproxil fumarate (TDF), little in vitro evidence was generated, no randomized trials for early treatment were done, and the drug was not considered for authorization. Yet, by the summer of 2020, observational evidence suggested a substantially lower risk for severe COVID-19 in TDF users compared with nonusers. The decision-making process for the launching of randomized trials for these 3 drugs is reviewed. Observational data in favor of TDF was systematically dismissed, even though no viable alternative explanations were proposed for the lower risk for severe COVID-19 among TDF users. Lessons learned from the TDF example during the first 2 years of the COVID-19 pandemic are described, and the use of observational clinical data to guide decisions about the launch of randomized trials during the next public health emergency is proposed. The goal is that gatekeepers of randomized trials make better use of the available observational evidence for the repurposing of drugs without commercial value.
Nanomedicine‐Based Therapeutics for Myocardial Ischemic/Reperfusion Injury
Authors: Xi Li, Wei Ou, Maodi Xie, Jing Yang, Qian Li, Tao Li
Journal: Advanced Healthcare Materials (2023)

Abstract Myocardial ischemic/reperfusion (IR) injury is a global cardiovascular disease with high mortality and morbidity. Therapeutic interventions for myocardial ischemia involve restoring the occluded coronary artery. However, reactive oxygen species (ROS) inevitably impair the cardiomyocytes during the ischemic and reperfusion phases. Antioxidant therapy holds great promise against myocardial IR injury. The current therapeutic methodologies for ROS scavenging depend predominantly on administering antioxidants. Nevertheless, the intrinsic drawbacks of antioxidants limit their further clinical transformation. The use of nanoplatforms with versatile characteristics greatly benefits drug delivery in myocardial ischemic therapy. Nanoplatform‐mediated drug delivery significantly improves drug bioavailability, increases therapeutic index, and reduces systemic toxicity. Nanoplatforms can be specifically and reasonably designed to enhance molecule accumulation at the myocardial site. The present review initially summarizes the mechanism of ROS generation during the process of myocardial ischemia. The understanding of this phenomenon will facilitate the advancement of innovative therapeutic strategies against myocardial IR injury. The latest developments in nanomedicine for treating myocardial ischemic injury are then discussed. Finally, the current challenges and perspectives in antioxidant therapy for myocardial IR injury are addressed.
Hyaluronic Acid‐Based Bioconjugate Systems, Scaffolds, and Their Therapeutic Potential
Authors: Niranjan G. Kotla, Isma Liza Mohd Isa, Aitor Larrañaga, Balaji Maddiboyina, Samantha K. Swamy, Gandhi Sivaraman, Praveen K. Vemula
Journal: Advanced Healthcare Materials (2023)

Abstract In recent years, the development of hyaluronic acid or hyaluronan (HA) based scaffolds, medical devices, bioconjugate systems have expanded into a broad range of research and clinical applications. Research findings over the last two decades suggest that the abundance of HA in most mammalian tissues with distinctive biological roles and chemical simplicity for modifications have made it an attractive material with a rapidly growing global market. Besides its use as native forms, HA has received much interest on so‐called “HA‐bioconjugates” and “modified‐HA systems”. In this review, the importance of chemical modifications of HA, underlying rationale approaches, and various advancements of bioconjugate derivatives with their potential physicochemical, and pharmacological advantages are summarized. This review also highlights the current and emerging HA‐based conjugates of small molecules, macromolecules, crosslinked systems, and surface coating strategies with their biological implications, including their potentials and key challenges discussed in detail.
VP2-2023: Dostarlimab+chemotherapy for the treatment of primary advanced or recurrent (A/R) endometrial cancer (EC): A placebo (PBO)-controlled randomised phase III trial (ENGOT-EN6-NSGO/GOG-3031/RUBY)
Authors: M.R. Mirza, D. Chase, B.M. Slomovitz, R.D. Christensen, Z. Novák, D. Black, L. Gilbert, S. Sharma, G. Valabrega, L.M. Landrum, L.C. Hanker, A. Stuckey, I.A. Boere, M. Gold, S.E. Gill, B.J. Monk, Z. He, S. Stevens, R.L. Coleman, M.A. Powell
Journal: Annals of Oncology (2023)
Emergence of consciousness from anesthesia through ubiquitin degradation of KCC2 in the ventral posteromedial nucleus of the thalamus
Authors: Jiang-Jian Hu, Yuexin Liu, Hongyu Yao, Boxu Cao, Huabao Liao, Ruodi Yang, Peng Chen, Xue-Jun Song
Journal: Nature Neuroscience (2023)
Specific regulation of BACH1 by the hotspot mutant p53R175H reveals a distinct gain-of-function mechanism
Authors: Zhenyi Su, Ning Kon, Jingjie Yi, Haiqing Zhao, Wanwei Zhang, Qiaosi Tang, Huan Li, Hiroki Kobayashi, Zhiming Li, Shoufu Duan, Yanqing Liu, Kenneth P. Olive, Zhiguo Zhang, Barry Honig, James J. Manfredi, Anil K. Rustgi, Wei Gu
Journal: Nature Cancer (2023)
Determinants of COVID-19 vaccine fatigue
Authors: Tanja A. Stamm, Julia Partheymüller, Erika Mosor, Valentin Ritschl, Sylvia Kritzinger, Alessia Alunno, Jakob-Moritz Eberl
Journal: Nature Medicine (2023)

There is growing concern that Coronavirus Disease 2019 (COVID-19) vaccine fatigue will be a major obstacle in maintaining immunity in the general population. In this study, we assessed vaccine acceptance in future scenarios in two conjoint experiments, investigating determinants such as new vaccines, communication, costs/incentives and legal rules. The experiments were embedded in an online survey (n = 6,357 participants) conducted in two European countries (Austria and Italy). Our results suggest that vaccination campaigns should be tailored to subgroups based on their vaccination status. Among the unvaccinated, campaign messages conveying community spirit had a positive effect (0.343, confidence interval (CI) 0.019-0.666), whereas offering positive incentives, such as a cash reward (0.722, CI 0.429-1.014) or voucher (0.670, CI 0.373-0.967), was pivotal to the decision-making of those vaccinated once or twice. Among the triple vaccinated, vaccination readiness increased when adapted vaccines were offered (0.279, CI 0.182-0.377), but costs (-0.795, CI -0.935 to -0.654) and medical dissensus (-0.161, CI -0.293 to -0.030) reduced their likelihood to get vaccinated. We conclude that failing to mobilize the triple vaccinated is likely to result in booster vaccination rates falling short of expectations. For long-term success, measures fostering institutional trust should be considered. These results provide guidance to those responsible for future COVID-19 vaccination campaigns.
Collateral sensitivity between tetracyclines and aminoglycosides constrains resistance evolution in carbapenem-resistant Klebsiella pneumoniae
Authors: Xinqian Ma, Wen Xi, Deqing Yang, Lili Zhao, Wenyi Yu, Yukun He, Wentao Ni, Zhancheng Gao
Journal: Drug Resistance Updates (2023)

The acquisition of resistance to one antibiotic may confer an increased sensitivity to another antibiotic in bacteria, which is an evolutionary trade-off between different resistance mechanisms, defined as collateral sensitivity (CS). Exploiting the role of CS in treatment design could be an effective method to suppress or even reverse resistance evolution. Using experimental evolution, we systematically studied the CS between aminoglycosides and tetracyclines in carbapenem-resistant Klebsiella pneumoniae (CRKP) and explored the underlying mechanisms through genomic and transcriptome analyses. The application of CS-based therapies for resistance suppression, including combination therapy and alternating antibiotic therapy, was further evaluated in vitro and in vivo. Reciprocal CS existed between tetracyclines and aminoglycosides in CRKP. The increased sensitivity of aminoglycoside-resistant strains to tetracyclines was associated with the alteration of bacterial membrane potential, whereas the unbalanced oxidation-reduction process of tetracycline-resistant strains may lead to an increased bacterial sensitivity to aminoglycosides. CS-based combination therapy could efficiently constrain the evolution of CRKP resistance in vitro and in vivo. In addition, alternating antibiotic therapy can re-sensitize CRKP to previously resistant drugs, thereby maintaining the trade-off. These results provide new insights into constraining the evolution of CRKP resistance through CS-based therapies.
Neuroblastoma arises in early fetal development and its evolutionary duration predicts outcome
Authors: Verena Körber, Sabine A. Stainczyk, Roma Kurilov, Kai-Oliver Henrich, Barbara Hero, Benedikt Brors, Frank Westermann, Thomas Höfer
Journal: Nature Genetics (2023)

Abstract Neuroblastoma, the most frequent solid tumor in infants, shows very diverse outcomes from spontaneous regression to fatal disease. When these different tumors originate and how they evolve are not known. Here we quantify the somatic evolution of neuroblastoma by deep whole-genome sequencing, molecular clock analysis and population-genetic modeling in a comprehensive cohort covering all subtypes. We find that tumors across the entire clinical spectrum begin to develop via aberrant mitoses as early as the first trimester of pregnancy. Neuroblastomas with favorable prognosis expand clonally after short evolution, whereas aggressive neuroblastomas show prolonged evolution during which they acquire telomere maintenance mechanisms. The initial aneuploidization events condition subsequent evolution, with aggressive neuroblastoma exhibiting early genomic instability. We find in the discovery cohort ( n = 100), and validate in an independent cohort ( n = 86), that the duration of evolution is an accurate predictor of outcome. Thus, insight into neuroblastoma evolution may prospectively guide treatment decisions.
Intrinsic activity development unfolds along a sensorimotor–association cortical axis in youth
Authors: Valerie J. Sydnor, Bart Larsen, Jakob Seidlitz, Azeez Adebimpe, Aaron F. Alexander-Bloch, Dani S. Bassett, Maxwell A. Bertolero, Matthew Cieslak, Sydney Covitz, Yong Fan, Raquel E. Gur, Ruben C. Gur, Allyson P. Mackey, Tyler M. Moore, David R. Roalf, Russell T. Shinohara, Theodore D. Satterthwaite
Journal: Nature Neuroscience (2023)
Pan-cancer analysis identifies tumor-specific antigens derived from transposable elements
Authors: Nakul M. Shah, H. Josh Jang, Yonghao Liang, Ju Heon Maeng, Shin-Cheng Tzeng, Angela Wu, Noah L. Basri, Xuan Qu, Changxu Fan, Amy Li, Benjamin Katz, Daofeng Li, Xiaoyun Xing, Bradley S. Evans, Ting Wang
Journal: Nature Genetics (2023)
Prospective, randomized, multicenter clinical study comparing a self-expanding covered stent to percutaneous transluminal angioplasty for treatment of upper extremity hemodialysis arteriovenous fistula stenosis
Authors: Bart Dolmatch, Timoteo Cabrera, Pablo Pergola, Saravanan Balamuthusamy, Angelo Makris, Randy Cooper, Erin Moore, Jonah Licht, Ewan Macaulay, Geert Maleux, Thomas Pfammatter, Richard Settlage, Ecaterina Cristea, Alexandra Lansky, Bart Dolmatch, Gerard Goh, Stewart Hawkins, Ewan Macaulay, Ian Spark, Rick de Graff, Hannes Deutschmann, Ralph Kickuth, Geert Maleux, Thomas Pfammatter, Levester Kirksey, Robert Mendes, John Aruny, Vagar Ali, Timoteo Cabrera, Pablo Pergola, Deepak Sharma, Erin Moore, Himanshu Shah, Amy Dwyer, Dominic Yee, Wang Teng, Randy Cooper, Saravanan Balamuthusamy, George Lipkowitz, Theodore Saad, Jonah Licht, Angelo Makris, Tim Rogers, Jason Burgess, Jeffrey Hoggard
Journal: Kidney International (2023)

Use of a covered stent after percutaneous transluminal angioplasty (PTA) was compared to PTA alone for treatment of upper extremity hemodialysis patients with arteriovenous fistula (AVF) stenoses. Patients with AVF stenosis of 50% or more and evidence of AVF dysfunction underwent treatment with PTA followed by randomization of 142 patients to include a covered stent or 138 patients with PTA alone. Primary outcomes were 30-day safety, powered for noninferiority, and six-month target lesion primary patency (TLPP), powered to test whether TLPP after covered-stent placement was superior to PTA alone. Twelve-month TLPP and six-month access circuit primary patency (ACPP) were also hypothesis tested while additional clinical outcomes were observed through two years. Safety was significantly non-inferior while six- and 12-month TLPP were each superior for the covered stent group compared to PTA alone (six months: 78.7% versus 55.8%; 12 months: 47.9% versus 21.2%, respectively). ACPP was not statistically different between groups at six-months. Observed differences at 24 months favored the covered-stent group: 28.4% better TLPP, fewer target-lesion reinterventions (1.6 ± 1.6 versus 2.8 ± 2.0), and a longer mean time between target-lesion reinterventions (380.4 ± 249.5 versus 217.6 ± 158.4 days). Thus, our multicenter, prospective, randomized study of a covered stent used to treat AVF stenosis demonstrated noninferior safety with better TLPP and fewer target-lesion reinterventions than PTA alone through 24 months.
Deep learning–based segmentation and quantification of podocyte foot process morphology suggests differential patterns of foot process effacement across kidney pathologies
Authors: David Unnersjö-Jess, Linus Butt, Martin Höhne, German Sergei, Arash Fatehi, Anna Witasp, Annika Wernerson, Jaakko Patrakka, Peter F. Hoyer, Hans Blom, Bernhard Schermer, Katarzyna Bozek, Thomas Benzing
Journal: Kidney International (2023)

Morphological alterations at the kidney filtration barrier increase intrinsic capillary wall permeability resulting in albuminuria. However, automated, quantitative assessment of these morphological changes has not been possible with electron or light microscopy. Here we present a deep learning-based approach for segmentation and quantitative analysis of foot processes in images acquired with confocal and super-resolution fluorescence microscopy. Our method, Automatic Morphological Analysis of Podocytes (AMAP), accurately segments podocyte foot processes and quantifies their morphology. AMAP applied to a set of kidney diseases in patient biopsies and a mouse model of focal segmental glomerulosclerosis allowed for accurate and comprehensive quantification of various morphometric features. With the use of AMAP, detailed morphology of podocyte foot process effacement was found to differ between categories of kidney pathologies, showed detailed variability between diverse patients with the same clinical diagnosis, and correlated with levels of proteinuria. AMAP could potentially complement other readouts such as various omics, standard histologic/electron microscopy and blood/urine assays for future personalized diagnosis and treatment of kidney disease. Thus, our novel finding could have implications to afford an understanding of early phases of kidney disease progression and may provide supplemental information in precision diagnostics.
Global burden of liver disease: 2023 update
Authors: Harshad Devarbhavi, Sumeet K. Asrani, Juan Pablo Arab, Yvonne Ayerki Nartey, Elisa Pose, Patrick S. Kamath
Journal: Journal of Hepatology (2023)

Liver disease accounts for two million deaths annually and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately two-thirds of all liver-related deaths occur in men. Deaths are largely attributable to complications of cirrhosis and hepatocellular carcinoma, with acute hepatitis accounting for a smaller proportion of deaths. The most common causes of cirrhosis worldwide are related to viral hepatitis, alcohol, and non-alcoholic fatty liver disease. Hepatotropic viruses are the aetiological factor in most cases of acute hepatitis, but drug-induced liver injury increasingly accounts for a significant proportion of cases. This iteration of the global burden of liver disease is an update of the 2019 version and focuses mainly on areas where significant new information is available like alcohol-associated liver disease, non-alcoholic fatty liver disease, viral hepatitis, and hepatocellular carcinoma. We also devote a separate section to the burden of liver disease in Africa, an area of the world typically neglected in such documents.
Factors Linked to Injection Interval Extension in Eyes with Wet Age-Related Macular Degeneration Switched to Brolucizumab
Authors: Mathew W. MacCumber, Charles C. Wykoff, Helene Karcher, Eser Adiguzel, Samriddhi Buxy Sinha, Saloni Vishwakarma, Andrew LaPrise, Franklin Igwe, Rita Freitas, Michael S. Ip, Marco A. Zarbin
Journal: Ophthalmology (2023)
Subclinical rejection-free diagnostic after kidney transplantation using blood gene expression
Authors: Richard Danger, Ludmilla Le Berre, Marion Cadoux, Clarisse Kerleau, Emmanuelle Papuchon, Hoa Le Mai, Thi-Van-Ha Nguyen, Pierrick Guérif, Emmanuel Morelon, Olivier Thaunat, Christophe Legendre, Dany Anglicheau, Carmen Lefaucheur, Lionel Couzi, Arnaud Del Bello, Nassim Kamar, Moglie Le Quintrec, Valentin Goutaudier, Karine Renaudin, Magali Giral, Sophie Brouard, Lionel Badet, Maria Brunet, Fanny Buron, Rémi Cahen, Ricardo Codas, Sameh Daoud, Valérie Dubois, Coralie Fournie, François Gaillard, Arnaud Grégoire, Alice Koenig, Charlène Lévi, Emmanuel Morelon, Claire Pouteil-Noble, Maud Rabeyrin, Thomas Rimmelé, Olivier Thaunat, Gilles Blancho, Julien Branchereau, Diego Cantarovich, Agnès Chapelet, Jacques Dantal, Clément Deltombe, Lucile Figueres, Raphael Gaisne, Claire Garandeau, Magali Giral, Caroline Gourraud-Vercel, Maryvonne Hourmant, Georges Karam, Clarisse Kerleau, Delphine Kervella, Christophe Masset, Aurélie Meurette, Simon Ville, Christine Kandell, Anne Moreau, Karine Renaudin, Florent Delbos, Alexandre Walencik, Anne Devis, Lucile Amrouche, Dany Anglicheau, Olivier Aubert, Lynda Bererhi, Christophe Legendre, Alexandre Loupy, Frank Martinez, Arnaud Méjean, Rébecca Sberro-Soussan, Anne Scemla, Marc-Olivier Timsit, Julien Zuber
Journal: Kidney International (2023)
A single approach to targeting transferrin receptor 2 corrects iron and erythropoietic defects in murine models of anemia of inflammation and chronic kidney disease
Authors: Violante Olivari, Simona Maria Di Modica, Maria Rosa Lidonnici, Mariam Aghajan, Celia Cordero-Sanchez, Emanuele Tanzi, Mariateresa Pettinato, Alessia Pagani, Francesca Tiboni, Laura Silvestri, Shuling Guo, Giuliana Ferrari, Antonella Nai
Journal: Kidney International (2023)